ABSTRACT
ObjectiveTo clarify the scientific validity of in vivo pharmacokinetic determination of the whole drug composition in Shenbai nanosuspension in rats， and to provide methodological guidance and theoretical basis for the in vivo study of multi-component complex system of traditional Chinese medicine（TCM） preparations. MethodThe concentration of the overall components， mainly total saponins and total polysaccharides in Shenbai decoction and Shenbai nanosuspension， was determined in rat plasma at different times by area under the absorbance-wavelength curve method（AUAWC）， and the concentration of individual ginsenoside Rg1 was determined by high performance liquid chromatography（HPLC）， and the methodology was verified. The pharmacokinetic parameters of the whole component were compared with those of ginsenoside Rg1 to evaluate the in vivo operational characteristics of the two preparations. ResultThe methodological investigations of AUAWC and HPLC were in accordance with the requirements. AUAWC analysis showed that the overall components in both the decoction group and the nanosuspension group showed a one-compartment model， with half-life（t1/2） of 2.43 h and 2.04 h， respectively. The relative bioavailability of Shenbai nanosuspension was 138.99%. HPLC assay showed that ginsenoside Rg1 in the decoction group and the nanosuspension group showed a two-compartment model， with distribution half-life（t1/2α） of 0.13 h and 2.55 h， and elimination half-life（t1/2β） were 14.28 h and 3.85 h， respectively. The relative bioavailability of Shenbai nanosuspension was 127.49%. Compared with Shenbai decoction， the time to peak（tmax）， peak concentration（Cmax） and area under the drug-time curve（AUC） of the overall components and ginsenoside Rg1 in Shenbai nanosuspension were increased. ConclusionThe established AUAWC can be used for the pharmacokinetic study of the overall components of TCM preparations， which is complementary to the results of individual components measured by HPLC， and can provide useful reference for the in vivo study of new dosage forms of TCM.
ABSTRACT
Objective: To compare with the contents of alkaline substances from four different prescription of formulations of traditional Chinese medicine (single aconite decoction, Jiangfu Decoction, Sini Decoction, and Shenfu Injection) with the same dose of aconite. Methods: Taken aconitine as the standard substance, the area under absorbance-wavelength curve (AUAWC) and absorption values of alkaline substances from four formulations, namely single aconite decoction, Jiangfu Decoction, Sini Decoction and Shenfu Injection (every concentration of aconite crude herb for 0.2 g/mL as the same dose), were obtained, respectively, which were determined by the method of AUAWC after the scanning for the wavelength from 200~600 nm and the method of bromocresol green colorimetric at 415 nm, and the data calculated were compared. Results: The results are accurate and reliable, and the methods of both AUAWC and bromocresol green colorimetric are feasible. The linear equations were Y = 0.145 42 X + 3.240 4, r = 0.999 3 for the AUAWC and Y = 0.008 63 X + 0.006 57, r = 0.999 5 for the bromocresol green colorimetric, respectively. The contents of alkaline substances from single aconite decoction, Jiangfu Decoction, Sini Decoction and Shenfu Injection were acquired through the method of AUAWC, which were 1 137.992, 2 907.120, 2 455.611, and 298.208 μg/mL, respectively, and the contents of aconitum alkaline substances were obtained by bromocresol green colorimetric with the concentration of 293.824, 447.767, 343.804 and 38.382 μg/mL, respectively. The content determined by the former method was much larger than that of the latter method, but the trend of the contents from two methods was the same, which was Jiangfu Decoction > Sini Decoction > single aconite decoction > Shenfu Injection. Conclusion: The contents of alkaline substances from different prescription of formulations of traditional Chinese medicine with the same dose of aconite are different, and the concentration of overall alkaline substances from AUAWC is more comprehensive than that of aconitum alkaline substances determined by bromocresol green colorimetric, which will provide more scientific theory interpretation for compatibility mechanism and dose-effect relationship as well as security research of Chinese medicine preparation of aconite.
ABSTRACT
Objective: The absolute bioavailability of the preparation of Chuanxiong Radix components in rats was simultaneously studied by two methods of area under absorbance-wavelength curve (AUAWC) and high performance liquid chromatography (HPLC), which would confirm the feasibility that AUAWC could be used to determine the absolute bioavailability of components of Chinese materia medica (CMM). Methods: Based on the random two-way cross-over design, 60 SD rats were given the injection of Chuanxiong Radix components by iv and the same amount of drug suspension of the tablet of Chuanxiong Radix components by ig, respectively. Blood samples were collected at various time points after the administration. Plasma concentration of the total components, sodium ferulate, and ligustrazine hydrochloride of the two preparations of Chuanxiong Radix components in rats was measured by AUAWC combined with HPLC. Pharmacokinetic parameters and absolute bioavailability were calculated by DAS 2.0 program and the data obtained by the two methods were compared. Results: After ig administration, AUC0-∞ of total components was (77.218±13.492) mg·min/L by AUAWC and AUC0-∞ of total component was (169.775±18.252) mg∙min/L for iv injection. The absolute bioavailability of tablet of ligustrazine hydrochloride were (69.134±4.853) and (16.422±2.584) mg∙min/L, respectively by HPLC. As for iv injection, AUC0-∞ of sodium ferulate and ligustrazine hydrochloride were (155.244±28.994) and (36.754±6.645) mg∙min/L, respectively. The absolute bioavailabilities of ig administration were 44.53% and 44.68%, respectively. The data obtained by AUAWC were similar to by HPLC. Conclusion: The method of AUAWC can be used to determine the absolute bioavailability on the mixed drugs in the tablet of Chuanxiong Radix components, which will be helpful to solve the problem that the total and individual drugs of the preparation can be coanalyzed together under the combination method of HPLC. It will provide better enlightenment to study the absolute bioavailability of the mixed drugs from Western compound chemicals or complex components in CMM.